The goal of the proposed research is to understand the molecular bases for regulation of immunoglobulin (heavy and light chain) biosynthesis. The method of approach involves the combined use of biochemical analysis and somatic cell genetics, and is based on the availability of a variety of immunoglobulin synthesis variants derived from mouse myeloma cell lines. By comparing the malignant cell lines and their variants with normal lymphocytes an attempt will be made to determine whether malignant transformation alters the regulation of immunoglobulin synthesis. Four major problems will be investigated. First, we will further characterize and attempt to determine the significance of a kappa light chain constant region fragment; this unique product is coded for by a different gene than the gene coding for the normal kappa light chain which is simultaneously expressed in MPC 11 myeloma cells. These studies are particularly relevant to the unique problems posed by the two gene-one polypeptide and allelic exclusion hypotheses. Second, we will determine the amino acid sequence of the amino-terminal precursor regions of a number of in vitro kappa light chains in order to gain insight into the genetic relationship(s) between the precursor, variable, and constant regions of kappa light chain genes. Third, we will use in vitro transcriptional and translational analyses, as well as somatic cell genetic analyses, to investigate the apparent coordinate regulation of heavy chain and light chain gene expression which occurs in some mouse myeloma cell lines. Fourth, we will analyze the regulation of immunoglobulin gene expression and B-cell differentiation with somatic cell hybrids formed between malignant Abelson virus-transformed mouse lymphomas and: 1) mouse myeloma cell lines and 2) normal, immunized spleen lymphocytes.